Weight-for-length and weight-for-age z scores were significantly closer to normal with protein hydrolysate formula at age 7.5 months, found Julie A. Mennella, PhD, and colleagues at the Monell Chemical Senses Center in Philadelphia.

These differences appeared to be due to faster weight gain from comparatively higher consumption of the cow's-milk formula despite both formulas containing the same number of calories per ounce, the researchers reported in the January issue of Pediatrics.

"We've known for a long time that infants who are formula-fed gain weight at a faster rate," Mennella told MedPage Today, comparing formula with the gold standard of breast feeding.

But these results suggest "you can't lump formula-fed infants into one group," she explained in an interview.

The babies in the study randomized to cow's-milk formula weighed over 2 pounds more at 7.5 months of age compared with those on protein hydrolysate formula, despite weighing the same at birth and study entry, she noted.

She cautioned pediatricians and parents against basing their formula choice on the study results, calling the findings "too early."

Further research will be needed to determine the long-term effects, the researchers concluded.

However, Mennella acknowledged that the extra weight gain could have important health impacts later in life.

"Emerging evidence is informing us that this early rate of growth during the first year of life can have long-term consequences, including increasing the risk for the development of obesity, diabetes, metabolic syndrome, and a variety of other diseases," she said in an interview.

Roughly 75% of formula-fed infants in the U.S. get cow's milk-based products, whereas the roughly twice-as-expensive protein hydrolysate formulas are typically reserved for infants allergic to cow's milk-based formula.

For hydrolysates, enzymes break down the milk proteins and then large peptides are filtered out, leaving free amino acids, similar to breast milk.

The trajectory of growth measured at monthly visits calculated against the World Health Organization growth standards indicated weight-for-age z scores of roughly 0.2 with protein hydrolysate formula compared with more than 1.0 with cow's-milk formula at 7.5 months (P<0.05 from 3.5 to 7.5 months), whereas 0 is considered normal.

Weight-for-length z scores were also significantly lower with the protein hydrolysate formula from ages 2.5 to 7.5 months (P<0.01).

Changes in these weight-for-age and weight-for-length z scores showed the same pattern (P<0.0001 and P<0.01 for the two measures, respectively), yielding slower weight-gain velocity with the protein hydrolysate formula (P<0.05).

Length-for-age was similar between the groups (P=0.86).

Excess weight gain in formula-fed babies had been chalked up to mothers missing satiety cues and overfeeding.

"This research calls that into serious question," Mennella said. "What we're finding is the type of formula that infants are feeding [on] is contributing to the faster weight gain."

Videotape of the infants being fed their assigned formula at each monthly visit showed that protein hydrolysate-fed infants consumed less to reach satiety (P=0.05) despite similar duration of feeding and their mothers rating the formulas as equally well-liked.

Further research is needed to determine what in the cow's-milk formula is present or absent compared with protein hydrolysate that could account for the difference, the researchers concluded.

They speculated in the paper, though, that the free amino acids "stimulate sensory receptors in the oral cavity and/or gastrointestinal tract, which, in turn, may serve as key signals for intake regulation and satiation."

The study was funded by the National Institutes of Health. Mead Johnson Nutritionals supplied the formulas.

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